Design of Resolving Agents Based on Crystal Engineering

Abstract

As a result of systematic studies on the optical resolution of racemates via crystallization, we have found that in many cases, common characteristic hydrogen-bond networks were formed in the less-soluble diastereomeric salts or conglomerates. Design of resolving/derivatizing agents could be achieved on the basis of the concept of crystal engineering, by which molecules were designed to achieve stable hydrogen-bond networks with target racemates.

Hydrogen-bonding sheets in crystals for chirality recognition: synthesis and application of (2S,3S)-2,3-dihydroxy- and (2S,3S)-2,3-dibenzyloxy-1,4-bis(hydroxyamino)butanes

“…1,2 Among acidic resolving agents, enantiopure monocarboxylic acids and arylglycolic acids generally form a helical hydrogen-bonding column with a twofold screw axis in the center (2 1 column) in less-soluble salt crystals with chiral primary amines. [3][4][5] In contrast, tartaric acid, a typical diacidic resolving agent, frequently forms a two-dimensional hydrogen-bonding sheet in less-soluble 1:1 salt crystals with chiral primary amines. 6 The sheet is fundamentally constructed by (1) hydrogen bonds between the carboxyl group of a tartaric acid molecule and the carboxylate group of a neighboring tartrate molecule, which forms an ionic pair with an ammonium group derived from a chiral amine, in a head-to-tail manner to afford a one-dimensional chain and 2) those between the carboxyl/carboxylate groups of a chain and the hydroxy groups of a neighboring chain.…”

Strategies in optical resolution: a practical guide

“…Resolving agents found by this approach, such as trans-53, proved to be useful for the resolution of substituted naphthylacetic acids as well. 54 3.12. Which enantiomer of the resolving agent should be used?…”

“…54 Thus, for the resolution of 11, analogues substituted at the aromatic ring of naphthyl-glycolic acid were found to be promising agents for almost all of the substituted analogues. Resolving agents found by this approach, such as trans-53, proved to be useful for the resolution of substituted naphthylacetic acids as well.…”

Direct asymmetric hydrogenation of α-keto acids by using the highly efficient chiral spiro iridium catalysts

“…14 On the basis of this work, we speculate that the same strategy seems to be working in the direct 50 hydrogenation of α-keto acids. Herein we report that the Ir/SpiroPAP (1) catalyzed direct asymmetric hydrogenation of αketo acids (2) to provide the chiral α-hydroxy acids (3) with excellent enantioselectivity (up to 99.2% ee) and high TON (as high as 50,000) under mild reaction conditions (Scheme 1).…”